5.9 Abstract - FUNCTIONAL GENOMICS (Core Group B) The Functional Genomics Shared Resource (FG) (Core Group B) enables Cancer Center members to rapidly perform large-scale genetic screens in cells. FG provides high-throughput screening (HTS) infrastructure, expertise, and services to perform both loss- and gain-of-function studies. In addition, the Core offers a variety of services to facilitate the screen follow up process including the production of high quality viral preparations, validation of RNAi reagents, and the creation of custom mutated cell lines for in vitro and in vivo target validation. Since its inception in 2006, Functional Genomics has continued to evolve and adapt to meet the specific needs of Cancer Center investigators. During the last funding period, the Core increased gene coverage to siRNAs targeting the whole genome, established cDNA library overexpression protocols as well as miRNA gain and loss of function screening. Lentiviral methods for functional studies were implemented to address biological questions in a wider range of cellular systems. The independent operational infrastructure of the Core has also been enhanced. FG currently occupies a dedicated laboratory with all the instrumentation needed for efficient preparation of cells and assays, while still additionally leveraging the capabilities of other Facilities such as High Content Screening, Genomics and Bioinformatics to expand its capabilities and utilize additional expertise. In addition, usage of the Core (a new Shared Resource at the previous renewal) has been significantly increased, with 29 Cancer Center members supported in the past year. The projects performed by FG range from cancer metabolism to screening to achieve mechanistic understanding of compounds with therapeutic potential. Over the last funding period, 40 projects have been either completed or are in progress, and the Core has supported 24 publications, with 9 additional publications anticipated during the next year. An important role of the Core is to evaluate and implement new technologies. Major areas of technical development under progress at FG include functional analysis of patient-derived primary tumor lines, adoption of 3D culture techniques in HT formats, and the applications of CRISPR-Cas9 based technologies. With the anticipated increase in demand of functional genomics services, the Core will continue to focus on genome- wide loss of function screening as primary tools while develop new technologies outlined above. FG will play a major role in the Center addressing questions in the areas of autophagy, stress, cancer metabolism, and epigenetics. Overall, FG-supported studies will lead to the identification of new therapeutic targets as well as enhance our understanding of mechanisms of drug efficacy and development of drug resistance in cancers.